Solution properties of a peptide are, in part, dependent on the physical and chemical characteristics of each amino acid that make up the peptide and the interaction of each amino acid with other amino acids in the polymer. Amino acids such as leucine, isoleucine, and valine impart hydrophobic character while amino acids such as lysine, histidine, and arginine are hydrophilic. The charge of the peptide, as determined by the acid or base characteristic of the amino acids, will affect solubility properties, depending on the ionization state of the functional group in a particular solvent. Further, hydrogen bonding, ionic, van der Waals, and hydrophobic interactions of the amino acids with the solvent and other amino acids of the polymer impart unique properties to the polymer as a whole.
Many peptides have limited solubility in aqueous solvents owing to the presence of hydrophobic amino acids, and thus may limit the bioactive delivery of such peptides in soluble form. In addition, the presence of hydrophobic domains in a peptide can modify solution behaviour through the hydrophobic effect, where exclusion of water molecules through interaction of hydrophobic domains causes aggregation of the peptide, thereby limiting its solubility and delivery as an active physiological agent. Interactions of excipients with the hydrophobic regions of such peptides can exacerbate the entropy driven aggregation.
The limited solubility of such peptides in aqueous solution and the formation of aggregates from the hydrophobic effect or excipient interactions complicate their delivery as bioactive agents, particularly where rapid dissolution is desirable. Liquid formulations in which the peptides are dissolved or suspended in an aqueous diluent, though available, may suffer from palatability problems due to the unpleasant taste of the peptide. Dilution of the peptide also limits the drug concentrations deliverable by ingestion of peptides dissolved in a liquid. Compressed forms, such as tablets, may provide concentrations sufficient to provide a therapeutic effect but can suffer from slow dissolution properties, particularly by formation of hydration spheres, which can act as barriers for access of solvent molecules to the peptide.
Thus, there is a need in the art for bioactive peptide compositions that overcome the difficulties posed by certain peptide properties, such as insolubility, and have the delivery characteristics to be an effective therapeutic treatment.